Epidemiological, Clinical, and Laboratory Characteristics of Acute Disseminated Encephalomyelitis in Children: A Retrospective Study

Objectives We aimed to study the precipitating factors, demographic data, clinical and radiological manifestations, electroencephalography and laboratory findings, as well as association with infections, immunization and incidence of relapse of acute disseminated encephalomyelitis (ADEM) in children admitted to Mofid Children Hospital, Tehran, Iran from Mar 2013 to Mar 2016. Materials & Methods A 3-yr retrospective review of 29 children with definite final diagnosis of ADEM in Mofid Hospital in Tehran, Iran was performed. The diagnosis was based on specified criteria, including a presumed acute demyelinating process with no history of unexplained neurological symptoms and at least one demyelinating lesion shown on magnetic resonance imaging without evidence of previous destructive white matter lesions. Results Overall, 29 children diagnosed as ADEM were studied in terms of demographic characteristics, clinical manifestations and laboratory findings in two groups according to their recurrence. The mean age of the patients with recurrence was less than those without it were. It was more common in females but the difference was not statistically meaningful. There was no relationship between the season of the first episode of the disease and the recurrence incidence. Moreover, the relationship between viral infections and recurrence was statistically non-meaningful. No relationship between the recurrence of ADEM and clinical manifestations, radiological and laboratory findings was found. Conclusion The reason for high rate of recurrence in our patients may be related to the younger age of children in our study.


Introduction
Acute disseminated encephalomyelitis (ADEM) is a kind of inflammatory demyelinating disease of the CNS which usually occurs secondary to an antecedent infection or immunization.
Although the pathophysiological mechanism of ADEM is unknown, it is thought to be a T-cell immune-mediated response to myelin basic protein triggered by infections or vaccination. The clinical manifestations are different in each patient characterized by an acute or subacute onset of multifocal neurologic disturbances that typically follow a monophasic course in which a wide range of neurological and non-neurological signs and symptoms has been reported such as fever, malaise, myalgia, headache, nausea and vomiting, meningismus, convulsions, cranial nerve palsies, ataxia and psychosis (1)(2)(3)(4)(5)(6)(7)(8)(9). ADEM is a kind of neurological disease, which predominantly affects children and young adults.
The diagnosis may become difficult because in 30% of cases, the first episode of ADEM subsequently evolves typical multiple sclerosis (MS) (8). The occurrence of recurrent periods and relapses in some of the patients make it difficult to distinguish from MS (2,9). Although recurrence may occur, the prognosis is usually good and most of the children make a full recovery (6). ADEM may occur in any age but it is often seen in average age of 5 to 8 yr and is mostly in male (15).
The definite diagnosis is not available by a kind of pathognomonic clinical or laboratory findings and patients usually has a normal brain computed tomography (CT) features. Magnetic resonance imaging (MRI) by showing high signal lesions of the same age on T2-weighted images will help us to make the diagnosis of ADEM. High signal lesions are usually seen in the subcortical white matter but there may be some lesions in the cerebellum, grey matter, basal ganglia, periventricular regions, brain stem, thalamus, midbrain or spinal cord (6,8,16,17).
Prescribing high dose methylprednisolone, dexamethasone, intravenous immunoglobulin (IVIG) and plasmapheresis are used to manage the patients diagnosed as ADEM (6,(18)(19)(20). The increasing rate of using MRI as a brain imaging in recent years has led to more correct diagnosis of ADEM in children which results in more effective treatments (6,21).
"The exact incidence of ADEM is not known but it has been reported approximately 0.4/10 5 /year among people less than twenty years old in San Diego County" (22). ADEM was more common in children population because of higher exposure to antigens and higher frequency of immunization and viral infections in children (9). Most of the studies about ADEM patients have been done on pediatric populations reported mostly in Caucasians (22).

Few large series of ADEM have been published in
Asian populations (22)(23)(24), and similar studies are scarce in Iran. Thus we tried to study the precipitating factors, demographic data, clinical and radiological Overall, 29 cases were entered our case-series study with the definite diagnosis of ADEM. Moreover, telephone interviewing was done carefully for each case in order to complete the data which was all classified in a chart questionnaire.
The data was recorded confidentially and informed consent was obtained from parents. Each person was characterized by a numerical code.  (Table 1). Table 2 shows clinical manifestations, EEG and MRI findings and Table 3 shows the laboratory findings.
In 9 patients (31%) recurrence occurred in which the mean period of time between the recovery after the first onset of the disease and its recurrence was No relationship between the recurrence of ADEM and clinical manifestations, radiological and laboratory findings was found. with or without recurrence. The mean age of the patients in our study was 56.07 months which was less than other studies (over 5 yr old) (26)(27)(28)(29)(30).
Male/ female ratio in our study was 1.23 which was consistent with previous studies (28,29,31).
In our study, the seasonal distribution of ADEM was equal, while in previous studies the most incidence of ADEM was in winter (10,32,33).
Seasonal priority in those studies may be justified by more incidence of febrile viral infections in winter incriminated for ADEM.
44.8% of the patients in our study had a history of a febrile infection last month before ADEM presentations but this amount was different in other studies (more than 70%) (4,5,8,10,27,29,32,34,35).
The current result of our study is consistent with the last study in Iran (46.4%) (9). History of febrile disease (mostly viral infections) has a small causal role in the incidence of ADEM in our country. Only 13.8% of the patients in our study had a history of vaccination in the last month before presentation of the disease which was the same as other studies (9,29,35).
The most common region of the brain lesions was subcortical This matter according to our study (51.7%) This result was similar to previous studies; Though , the rate of sub cortical white matter involvement in the preview studies was more than ours(more than 80%) (9,10,29,32,34).
Motor deficit and seizure were the most common signs in our patients with the incidence rate of 44.8% separately, and consciousness alterations, ataxia, and headache were the next common signs, respectively. In previous studies motor deficit was also the most common sign; Ataxia and consciousness alterations were reported as most common signs after motor deficit (4,6,9,23,26,34).
These results showed a more incidence of seizure in our study.